Keto analogs of essential amino acids have been proposed for use in human nutrition as partial or complete substitutes for the corresponding amino acids, including, for example, leucine, isoleucine, methionine, phenylalanine, and valine. Originally, the use of such keto analogs was proposed by Dr. MacKenzie Walser as supplementation to protein-reduced diets in uremia. See, for example, Walser et al. J. Clin. Inv. (1973) 52:678-690. Further experiments by Walser and associates demonstrated a nitrogen sparing effect from mixtures of branched-chain keto acids. Saiper and Walser, Metabolism (1977) 26:301-308. Patents have issued to Walser on the use of keto analogs of essential amino acids for promotion of protein synthesis and suppression of urea formation in humans. (U.S. Pat. Nos. 4,100,161 and 4,101,293). A recent review summarized existing knowledge with respect to the administration of branched-chain keto acids to humans. "New Aspects of Clinical Nutrition," pp. 319-324 (Karger, Basel, 1983).
The keto acid analog of L-leucine is alpha-ketoisocaproate (KIC) which is also sometime referred to as "keto-leucine." KIC does not have L and D forms as does leucine. It is known that there is an interconversion of circulating KIC and leucine. Published studies have demonstrated that KIC can be substituted in animal diets for leucine providing that larger molar amounts of KIC are used.
Chawla et al. reported that weight loss by rats being fed a diet deficient in leucine could be prevented by adding KIC to the diet, but the efficiency of substitution was only 20 to 27%. J. Nutr. (1975) 105:798-803. Other studies in rats have demonstrated that KIC is utilized less efficiently than leucine. Boebel et al. reported that the efficiency of KIC was only about 56% with reference to leucine. Boebel and Baker, J. Nutr. (1982) 112:1929-1939. Chow et al. obtained comparable results, reporting that substitution of KIC for leucine reduced feed efficiency by approximately 33%. Chow and Walser, J. Nutr. (1974) 104:1208-1214.
Walser and associates have published a study of the oral dosing of KIC to rats in which an increased efficiency of utilization of nitrogen was apparently observed. Abras and Walser, Am. J. Clin. Nutr. (1982) 36:154-161. There are no known reports describing the feeding of KIC to domestic lactating mammals.